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Hence, the present study was undertaken to explore the cardio protective potential of esculetin against isoproterenol induced myocardial toxicity in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The treatment schedule was fixed for 28\u2009days and the rats were divided into five groups of six each. Rats of group I received the normal saline and served as normal control, group II was received ISO (100\u2009mg\/kg body weight) for last two consecutive days of the study and served as disease control. Groups III and IV received esculetin 10 and 20\u2009mg\/kg body weight respectively once a day per oral for 28\u2009days along with ISO for last two consecutive days of the study. Cardiac biomarkers such as CK-MB and LDH, membrane bound Na+ \/K+ ATPases activity, myocardial lysosomal enzymes activity and tissue antioxidants status were estimated in the heart tissue samples. The histopathological changes in the myocardium were also assessed. Further, DPPH assay was done to evaluate the free radicals scavenging potential of esculetin. Cytoxicity assay, intracellular ROS levels by DCFDA assay and m-RNA expression of TNF-\u03b1, IL-6 and NF-\u03baB by quantitative RT-PCR in H9c2 cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The increased levels of CK-MB, LDH, LPO, myocardial lysosomal enzymes and membrane bound Na+ \/K+ ATPase levels by ISO administration was significantly increased with concomitant decrease in tissue antioxidant enzymes such as GSH, Catalase, and SOD. Pre-treatment with esculetin for 28\u2009days has significantly decreased the levels of cardiac bio-markers, lysosomal enzymes, membrane bound Na+ \/K+ ATPase levels as well as Lipid peroxides which is in contrary to the ISO group. Amelioration of the antioxidant levels were also found in esculetin treated groups. Histopathological examination of heart reveals that myocardial degeneration, mononuclear cell infiltration was noticed in ISO treated rats, whereas the same was restored with esculetin treatment. In H9C2 cell lines esculetin could effectively reduced intracellular ROS inhibition and m-RNA expression of pro-inflammatory cytokines including TNF-\u03b1, IL-6 and NF-\u03baB to prevent apoptosis or cell necrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study provides the evidence of cardioprotective potentials of esculetin against isoproterenol induced myocardial infarction by antioxidant and myocardial membrane stabilization along with in vitro protection from arsenic induced ROS cell necrosis or apoptosis in H9C2 cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-021-00510-0","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:03:18Z","timestamp":1626307398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Exploring cardioprotective potential of esculetin against isoproterenol induced myocardial toxicity in rats: in vivo and in vitro evidence"],"prefix":"10.1186","volume":"22","author":[{"given":"Chitikela P.","family":"Pullaiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod K.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma","family":"Rayapu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narasimha Kumar","family":"G V","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thyagaraju","family":"Kedam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"issue":"5","key":"510_CR1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S1875-5364(14)60042-X","volume":"12","author":"AA Zaki","year":"2014","unstructured":"Zaki AA, Hashish NE, Amer MA, Lahloub MF. 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Animal experimental protocols used in the present study were approved by Institutional Animal Ethical Committee of Sri Padmavathi School of Pharmacy (SPSP\/CPCSEA\/IAEC-1016\/a \/2015\/009), constitute as per the directions of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India. The further methods and procedures adopted in the study are in agreement with appropriate guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and declaration"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}